Microchimerism and Hyporesponsiveness Induced by Intraportal Injection of Donor Spleen Cells in Rats

Abstract

It is controversial whether or not microchimerism (MC) is responsible for the induction and maintenance of donor-specific tolerance. We have shown that intraportal injection (i.p.) of donor splenocytes induces a long-term graft survival of liver and heart in rats. In this study, we examined by polymerase chain reaction (PCR) the status of MC in the liver, spleen, and blood of rat cardiac recipients following i.p. or intravenous injection (i.v.) of donor splenocytes. Male DA (RTl a ) and Wistar (RTl k ) rats were used as donors and recipients, respectively. Heterotopic heart transplantation was performed 10 days after i.p. or i.v. injection of 5 × 10 7 DA spleen cells. DA cardiac allografts were rejected with a mean survival time (MST) of 11.9 ± 1.6 (n = 10) days in nontreated recipients. Injections (i.v.) led to no significant prolongation of graft survival (MST: 11.2 ± 1.9 days, n = 6), while i.p. injection induced a significant prolongation of graft survival (MST: 18.6 ± 1.5 days, n = 5) over the control. Either i.p. or i.v. injection alone resulted in systemic MC in these organs throughout the observation time over 60 days. MC was detected in the spleen, liver, and blood of cardiac recipients 7 days after transplantation and also even after cessation of cardiac heartbeat 21 days after transplantation. This was the case with either i.p. or i.v. group, which showed MC on day 7 after transplantation and persistent MC after cessation of the heartbeat. These data suggest that the presence of MC in the liver, spleen, and the blood of transplant recipients may not be responsible for immunological unresponsiveness to donor antigens.